He Ying, Cheng Yun, Chen Miao, Shi Lei, Chen Tao, Chen Huajun, Zhang Xin
Department of Intensive Care Unit, Zunyi Medical College Affiliated Hospital Huichuan District, Zunyi, Guizhou, China.
Department of Emergency, Zunyi Medical College Affiliated Hospital Huichuan District, Zunyi, Guizhou, China.
Int J Clin Exp Pathol. 2017 Oct 1;10(10):10315-10324. eCollection 2017.
Acute respiratory distress syndrome (ARDS) is a condition characterized by acute inflammation in the lungs. Apoptosis of alveolar epithelial type II (ATII) cells contributes to the initiation and progression of the disease. miRNAs are tightly regulated and their dysregulation plays an important role in human diseases. One such miRNA, miR-21 is shown to be involved in several different diseases. However, its role in ARDS is still not known. Here, we hypothesize that miR-21-5p inhibits apoptosis in ATII cells and protects against ARDS. In the present study, 50 μM HO was used to induce ATII cell damage to simulate ARDS . CCK-8 assay was performed to detect cell proliferation and flow cytometry was used to evaluate cell apoptosis. A dual-luciferase assay was performed to confirm whether miR-21 directly targeted the programmed cell death 4 (PDCD4) mRNA. Here, we found that ATII cell apoptosis increased after treatment with 0.5 mM HO. Overexpression of miR-21 or knockdown of PDCD4 promoted ATII cell proliferation and inhibited ATII cell apoptosis after treatment with HO. We further confirmed that miR-21 regulates PDCD4 expression by targeting its three prime untranslated region (3'-UTR). Our results suggest that miR-21 potentially antagonizes oxidant-mediated apoptosis in alveolar epithelial type II cells. These findings provide new insights in understanding the process of ARDS and also provide a potential target for the treatment of ARDS.
急性呼吸窘迫综合征（ARDS）是一种以肺部急性炎症为特征的病症。肺泡Ⅱ型上皮（ATII）细胞凋亡促成了该疾病的发生和发展。微小RNA（miRNA）受到严格调控，其失调在人类疾病中起重要作用。其中一种miRNA，即miR-21，已被证明与多种不同疾病有关。然而，其在ARDS中的作用尚不清楚。在此，我们假设miR-21-5p抑制ATII细胞凋亡并预防ARDS。在本研究中，使用50μM HO诱导ATII细胞损伤以模拟ARDS。进行CCK-8测定以检测细胞增殖，并使用流式细胞术评估细胞凋亡。进行双荧光素酶测定以确认miR-21是否直接靶向程序性细胞死亡4（PDCD4）mRNA。在此，我们发现用0.5 mM HO处理后ATII细胞凋亡增加。miR-21过表达或PDCD4敲低促进了HO处理后ATII细胞增殖并抑制了ATII细胞凋亡。我们进一步证实miR-21通过靶向其3'非翻译区（3'-UTR）来调节PDCD4表达。我们的结果表明，miR-21可能拮抗氧化剂介导的肺泡Ⅱ型上皮细胞凋亡。这些发现为理解ARDS的发病过程提供了新的见解，也为ARDS的治疗提供了潜在靶点。
